An Overview of pellets

Pellets are small spherical free flowing units with improved flow properties and flexibility in formulation development and manufacture. Their size and shape allow their administration as injections and also for oral drug delivery. Various methods of pelletization are balling, drug layering, extrusion-spheronization, spray drying, spray congealing are available. They can be used to design various customized release profiles. In this presentation, various applications and advantages of pellets were discussed along with their manufacturing methods especially drug layering and extrusion-spheronization Key words: Pellets, Extrusion-spheronization, Drug layering, coating

Comments

hi ,
you have mentioned in the extrusion spheronization technique the polymer can be applied either with drug or at last step as barrier coat. Does it have any effect in drug release pattern if so in what way and which releases the drug fast.

Thank you for your query. If the polymer is taken along with drug in extrusion-spheronization, it gets embeded in polymer matrix similar to our microsphere. Otherwise, polymer can be coated on the pellet similar to our microcapsule. Definitely, it will have effect on the release mechanism and drug release profile that in turn depends upon the concentration and nature of polymer taken and of course the nature of drug.

Do you think Is it possible to construct a wall without a brick only with cement and sand and apply paint on it? Similarly it is not possible to coat a small individual drug particle in a coating pan uniformly

Dear G. Sailesh,
As we know pelletization is preferred over other coating method, but it has several things to monitored and manage starting from process to equipment variables. I wanna know which are the Process Analytical Technology variables monitored under this?
Reagrds

Pelletization is different from coating. Formation of pellets is pelletization which can be done by extrusion-spheronization, drug layering, balling, spray congealing. Coating can be done on pellets. "Process analytical technology(PAT)" is a part of Quality by design(Qbd) initiated by FDA which says that quality is to be built into product rather than testing it. It literally means control of various critical variables that are likely to effect the final quality by real time monitoring. For example, if we consider the coating process, critical variables are coating thickness, diameter, agglomeration that has to be monitored and controlled during the process itself. In pelletization (extrusion-spheronization)polymorphic changes, hydrate formation are some of the variables that must be considered during each and every step like blending, granulation, extrusion, spheronization. Various spectroscopic, digital imaging techniques help in achieving the objective of PAT.
REFERENCES:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati...
Mozina M, Tomazevic D, Leben S, Pernus F, Likar B. Digital imaging as a process analytical technology tool for fluid-bed pellet coating process. Eur J Pharm Sci. 2010 Sep 11;41(1):156-62. Epub 2010 Jun 9.
Perez-Ramos JD, Findlay WP, Peck G, Morris KR. Quantitative Analysis of Film Coating in a Pan Coater Based on In-Line Sensor Measurements. AAPS PharmSciTech. 2005; 6(1): E127-E136
Sandler N, Rantanen J, Heinamaki J, Romer M, Marvola M, Yliruusi J. Pellet Manufacturing by Extrusion-Spheronization Using Process Analytical Technology. AAPS PharmSciTech. 2005; 6(2): E174-E183.

Process of making drugs into pellets(pelletization). Various techniques are extrusion-spheronization, drug layering on to NP seeds, balling, agitation, spray congealing, spray drying etc. Reduced dose dumping: releasing of drug at once called dose dumping. Main reason is due to failure of coating. In case of pellets, failure of coating on one pellet will not effect the release of drug preventing dose dumping.

All the questions raised by you were explained in my presentation (with voice). Anyways, increased bioavalibality is due to micro metre range of particles. Intra individual variation: Pellets have good flow properties and they behave is liquid. They can flow even if the pyloric sphincter is open or closed. So variation in bioavailability due to food effects is reduced. Similarly GI motility will have no effect on absorption of drug from pellets reducing inter individual variation (between two persons). Reduced local irritation: They will be in continous movement and there will be no accummulation at a particular region. So the irritation caused by irritant drugs is reduced.

For extrusion spheronization: suitable for only high dose, have to optimize equipment related variables for both extruders and spheronizers, expensive. Drug layering: suitable to only low dose drugs, requires sophisticated equipment like fluidized bed coating to carry out the process effectively. It is difficult to compress pellets into tablets as it may damage coating. Sometimes, organic solvents have to be used as all the polymers may not be soluble in aqueous vehicle. Commercially, aqueous dispersions of water insoluble polymers are available (surelase, aquacoat- ethylcellulose dispersions).

Pellet quality is influenced by number of variables like nature of starter seeds, type of technique employed, moisture content of starter seeds, nature of active ingredient, excipients used, equipment used etc.